Calcium ions are implicated in the sequence of events which are involved in neurotransmitter release. Ethanol can influence neurotransmitter release particularly in dopamine and norepinephrine. However, recent studies on synaptosomal calcium uptake by ethanol have shown opposite results. In addition it has been indicated that humans usually do not develop significant temperature changes during acute ethanol intoxication or withdrawal and that the results of experiments with rodents in the absence of appropriate temperature controls may not be relevant to humans. Certain biochemical and physiological observations in rodents may be attributed to hypothermia rather than to ethanol itself. It also has been stated that this concept can be extended to in vitro work with subcellular fractions obtained from animals that were hypothermic during acute or prolonged administration of ethanol. In light of the above information it is the intent of this research proposal to carefully examine the effects of ethanol on central regional synaptosomal calcium influx, during depolarized-dependent uptake of calcium and nondepolarized uptake of calcium. The sections of the brain used are the cortex, hypothalamus, striatum and cerebellum. Ethanol is administered acutely in a dose-dependent fashion (1 to 5 g/kg, i.p.). Furthermore, animals which are functionally tolerant to ethanol are studied. Functional tolerance to ethanol is produced in animals by a 24 hr inhalation period. Forty-eight hours after removal from the inhalation chamber, the animals are assessed for tolerance to the hypothermic effect of ethanol. Blood ethanol concentrations and body temperatures are determined at selected intervals in animals during acute and functional tolerance experiments. In all experiments outlined in the research proposal in which ethanol-induced hypothermia occurs in animals, a corresponding experiment is performed in which ethanol-induced hypothermia is prevented in the animals by elevating their environmental temperature. The design of such experiments appears to be very pertinent, if the data derived from rodents is to be extended to humans, and have any relevance.